Cortical spreading depression (CSD) in acute brain injury, including stroke, subarachnoid hemorrhage, and severe traumatic brain injury has significant clinical (3.2M patients/year) and economic importance (>$34B/year). A major limitation to current assessment of CSD is that it can only be observed with cortical electrodes requiring an invasive craniotomy. Thus only a small fraction of the most critically injured patient are monitored. We propose to develop a system that reliably detects CSDs with a non-invasive, scalp-mounted sensor array using direct-current electroencephalography (DC-EEG). Whereas conventional AC-coupled EEG is widely used clinically, it is not optimal for detecting the slowly moving DC-potential wave of CSD. In contrast, the underused technology of DC-coupled EEG is ideally suited for CSD detection. We aim to design, build, and validate a scalp-mounted, CSD-detection system by first optimizing the sensor array using computer simulation and creating software to process the signals and detect the CSDs. Our preliminary numerical simulations of CSD detection from the scalp agree well with the limited published data and indicate that propagation of the CSD is detectable with a sufficiently dense array. Specific Aim 1 involves the computer simulation of scalp potentials generated by CSDs of varying shapes and propagation patterns which will allow for the virtual design of the sensor array and the development of detection software. Specific Aim 2 involves prototype development, including the sensor array and user interface. Specific Aim 3 entails the testing of the device in normal control subjects and validating it using patients with acute brain injury in the Neuro-Intensive Care Unit (Neuro-ICU) who is known to exhibit CSD. In achieving these three Specific Aims we will reach five milestones: 1) the virtual design of the sensor system; 2) a software package for detection and analysis of CSDs; 3) a functioning prototype array; 4) a graphical user interface; and 5) human validation of the prototype. In Phase II, our primary goal will be to develop a marketable device for acute brain injury in the Neuro-ICU. Phase II will also test whether use could be expanded to include other conditions where CSD is hypothesized to occur, but which cannot currently be detected without our device (e.g. concussion, acute brain injury patients in emergency situations). From the use of our device in the Neuro-ICU (~20 times the number of those with a craniotomy), we estimate a potential market of 60K US customers that could generate $7M/year in revenue with a 5% market share. Our team combines individuals with expertise in electrical hardware and software design, EEG electrode development and implementation, numerical modeling and virtual design, and clinical and experimental investigation of CSD in brain injury. This expertise will allow us to produce this device through solid engineering principals. The direct and non-invasive assessment of CSD, as a primary neuropathological mechanism, would allow therapeutic targeting to improve outcomes in acute brain injury patients with CSDs, and possibly, after SBIR Phase II, provide an objective assessment of concussion.